The following discussion of the background of the invention is merely provided to aid the reader in understanding the invention and is not admitted to describe or constitute prior art to the present invention.
Florfenicol is a structural analog of chloramphenicol and thiamphenicol, having a fluorine atom instead of the hydroxyl group located at C-3 in the structure of chloramphenicol and thiamphenicol. Bacterial resistance to chloramphenicol and thiamphenicol is usually attributed to acetylation of the 3′ hydroxyl group by the action of chloramphenicol acetyl transferase. Since florfenicol does not possess the 3′ hydroxyl group such a mechanism of inactivation is not possible with florfenicol, thus making florfenicol a highly useful antibiotic.
Florfenicol is active against a variety of microorganisms including Citrobacter, Proteus mirabilis, Proteus sp., Shigella, Salmonella, Providencia, Bacteroides, Staphylococcus aureus, Enterococci, Pasteurella haemolytica, Pasteurella multocida, Haemophilus somnus, and Haemophilus influenza. Conversely, Serratia marcescens, Pseudomonas aeruginosa, and Acinetobacter, have been found to be resistant to florfenicol. Literature suggests that typical MICs (minimum inhibitory concentrations) of florfenicol for various bacteria range from 0.3-1 μg/ml.
Dosage schedules of antibiotics are designed to maintain serum or tissue levels above the MIC for the target organisms for a period of time sufficient to clear the infection. Drugs that are cleared rapidly must be administered more often to maintain effective levels. In the case of some highly hydrophilic drugs, the drugs are cleared from the system so rapidly that their use requires multiple daily doses. Therefore, there is a need for increasing the effectiveness of known hydrophilic antibacterial compounds, such as florfenicol.